This is a revised competing continuation application for a research program whose long-term objective is to develop and evaluate imaging method alternatives to current practice that (i) increase the frequency and accuracy with which breast cancer can be detected and diagnosed and (ii) improve the prediction and monitoring of disease progression/regression during treatment and follow-up periods of clinical care. The Program combines technological developments with broad-based clinical studies designed to establish the likelihood that four emerging modalities (1) Magnetic Resonance Elastography (MRE), (2) Electrical Impedance Spectroscopy (EIS), (3) Microwave Imaging Spectroscopy (MIS) and Near Infrared Spectral Imaging (NIR) can contribute, either alone or in combination, to breast imaging for (a) risk assessment, (b) early detection, (c) differential diagnosis, (d) treatment prognosis and (e) therapy monitoring. In the proposed second 5-year period of funding, the program expects to generate sufficient evidence to allow convincing estimates of the likely role of these breast imaging alternatives for differential diagnosis and pilot data in support of a role in treatment prognosis and therapy monitoring that would inform decision-making on initiation of larger clinical trials in any or all of these areas. The research is conceptualized around technical and clinical strategic plans which thematically integrate the Program. Specifically, the technical strategic plan for renewal centers (1) continued modality-specific advancement of the imaging systems, (2) coregistration with conventional imaging studies through a mixture of novel hardware and software based platform integrations and (3) property measurements on breast tissues at time of .surgery and prior to histopathology which have been imaged previously with the alternative methods. The clinical strategic plan identifies study designs which target: (1) the imaging of screening abnormalities recommended for biopsy, (2) the imaging of palpable masses on clinical breast exams, and (3) the imaging of locally-advanced cancers receiving neoadjuvant therapy. Structurally, the Program revolves around the four Project components, one responsible for each imaging modality, supported by Computational, Clinical and Administrative Core units that serve to bond the Project components through the programmatic themes of (i) deploying breast imaging alternatives in common cohorts of women, (ii) realizing breast imaging strategies which offer new types of property contrast and functional information to improve clinical decision-making, and (iii) exploiting model-based image reconstruction to estimate the physical properties of interest.